Affective deficits and pain insensitivity in schizophrenia

Affective deficits have long been considered a prominent feature of schizophrenia and play a central role in recent theory and research on the pathophysiology of this disorder. However, it has recently been argued that current approaches to the conceptualization and assessment of affective flattening in schizophrenia are confounded by the social and neuromotor deficits that are also prevalent in this disorder. Insensitivity to pain in individuals with schizophrenia — a phenomenon that has been reported frequently but never systematically investigated — provides one approach to examining affective flattening unconfounded by social and neuromotor deficits. Two studies are described in which signal detection theory measures of thermal pain sensitivity were examined in patients with schizophrenia, mood disorder, and normal controls; in addition, in the patients with schizophrenia, the relationships between these measures and measures of affective deficits were examined. Patients with schizophrenia had significantly poorer sensory discrimination of painful thermal stimuli than control subjects, but did not differ from controls with respect to their response criterion for reports of pain; patients with mood disorder had a significantly higher (i.e., more stoical) criterion for reports of pain than controls. As predicted, among the patients with schizophrenia, higher response criterion was significantly correlated with greater affective flattening and less intense affective experience (as well as with fewer positive symptoms and poorer premorbid adjustment). The results of these studies suggest that pain insensitivity in schizophrenia may reflect affective as well as sensory abnormalities, and that pain insensitivity in schizophrenia may provide a method for studying affective flattening in this disorder that is relatively independent of the social and neuromotor deficits that confound existing measures of this symptom. Continued examination of the relationship between pain insensitivity and affective deficits in schizophrenia is also important because numerous clinical reports have suggested that pain insensitivity is detrimental to health and can have life-threatening consequences in individuals with this disorder.This research was supported, in part, by research grants from the National Institute of Neurological Disorders and Stroke to Robert H. Dworkin (NS-30714) and W. Crawford Clark (NS-09263, NS-20248).     

Can I trust you? Negative affective priming influences social judgments in schizophrenia

Successful social interactions rely on the ability to make accurate judgments based on social cues as well as the ability to control the influence of internal or external affective information on those judgments. Prior research suggests that individuals with schizophrenia misinterpret social stimuli and this misinterpretation contributes to impaired social functioning. We tested the hypothesis that for people with schizophrenia, social judgments are abnormally influenced by affective information. Twenty-three patients with schizophrenia and 35 healthy control participants rated the trustworthiness of faces following the presentation of neutral, negative (threat-related), or positive affective primes. Results showed that all participants rated faces following negative affective primes as less trustworthy than faces following neutral or positive primes. Importantly, this effect was significantly more pronounced for participants with schizophrenia, suggesting that schizophrenia may be characterized by an exaggerated influence of negative affective information on social judgment. Furthermore, the extent that the negative affective prime influenced trustworthiness judgments was significantly associated with patients' severity of positive symptoms, particularly feelings of persecution. These findings suggest that for people with schizophrenia, negative affective information contributes to an interpretive bias, consistent with paranoid ideation, when judging the trustworthiness of others. This bias may contribute to social impairments in schizophrenia.     

On the broad applicability of the affective circumplex: representations of affective knowledge among schizophrenia patients

Abstract - Studies of affective experience are guided by the assumption that the structure of affect generalizes across people. Yet this assumption has not been tested among educationally and economically diverse community residents or among individuals with psychopathology. This study explicitly examined the broad applicability of the valence-arousal circumplex and whether schizophrenia patients and nonpatients have comparable knowledge structures of affective phenomena. Patients and nonpatients completed similarity ratings of 120 pairs of affect words. Similarity judgments were analyzed separately for each group using a multidimensional scaling procedure, and solutions were compared. Results revealed the same two-dimensional valence-arousal solution for schizophrenia patients and nonpatients, although there were subtle differences between the groups. These findings provide additional evidence that the circumplex model is a useful formalism for representing affective phenomena across diverse populations, and they bolster confidence in existing interpretations of schizophrenia patients' reports of affective experience.     

Clinical correlates of anhedonia and perceptual aberration in first-episode patients with schizophrenia and affective disorder.

We examined the association between scales measuring physical anhedonia, social anhedonia, and perceptual aberration and premorbid functioning, clinical state, and current level of adjustment in 91 psychotic subjects. The patients were examined at the onset of their first psychotic episode and again 18 months later. For patients with schizophrenia, anhedonia was significantly related to premorbid functioning. No association was found between the scales and clinical state or level of adjustment at intake or follow-up. In affective disorder patients, no correlation was found between premorbid functioning (a stable characteristic) and scale scores, but moderately large correlations emerged between the scales and clinical state and level of adjustment at both assessment times. These results suggest that schizophrenic and affective disorder patients endorse items on these scales for different reasons. We hypothesize that for patients with schizophrenia, the scales assess enduring personality characteristics, whereas for the affective disorder patients, they assess clinical condition at the time of testing.     

On "risk" and reward: investigating state anhedonia in psychometrically defined schizotypy and schizophrenia

Anhedonia, defined as dysfunction in the experience of pleasant emotions, is a hallmark symptom of the schizophrenia spectrum. Of interest, it is well documented that patients with schizophrenia, at least as a group, do not show reductions in their state experience of pleasant stimuli. However, there is emerging evidence to suggest that individuals with schizotypy--defined as the personality organization reflecting the latent vulnerability for schizophrenia--do show these state deficits. This is paradoxical in that schizophrenia reflects a more pathological state in virtually every conceivable domain as compared with schizotypy. The present study examined self-reported affective reactions to neutral-, bad-, and good-valenced stimuli in individuals with psychometrically defined schizotypy and schizophrenia. Two separate control groups were also included, comprising psychometrically defined controls and stable outpatients with affective disorders. With no exceptions, the schizotypy group reported significantly less pleasant affect for each of the three conditions than each of the other groups. Conversely, the schizophrenia group did not statistically differ from the control groups for any of the conditions. Within both the schizotypy and schizophrenia groups, severity of negative symptoms/traits was associated with less pleasant report. We found that individuals with prominent negative symptoms and traits from the schizophrenia and schizotypy groups resembled each other in terms of state anhedonia. The present findings did not appear to reflect comorbid depression or anxiety. Our discussion centers on this apparent paradox in the schizophrenia spectrum--that individuals with schizotypy exhibit state anhedonia, whereas patients with schizophrenia do not.     

Contradictions of emotion in schizophrenia

This paper considers contradictory features of emotional or affective experience and expression in schizophrenia in light of the “Kretschmerian paradox”—the fact that schizophrenia-spectrum patients can simultaneously experience both exaggerated and diminished levels of affective response. An attempt is made to explain the paradox and explore its implications. Recent research on emotion in schizophrenia is reviewed, including subjective reports, psychophysiological measures of arousal or activation, and behavioural measures, focusing on flat-affect and negative-symptom patients. After discussing relevant concepts and vocabulary of emotion (“affect”, “emotion”, “mood”, “feelings”, the “passions”), the need for a phenomenological approach focusing on subjective experience is proposed. Four modes of nonparanoid experience in schizophrenia are discussed: Bodily Alienation, Disengagement, Unworlding, and Subjectivisation. Each mode involves withdrawal from functional contexts—temporal, practical, and interpersonal—normally associated with emotional reactivity and expression; each may be accompanied by forms of non-emotional affectivity no less intense than the emotions they replace. Possible relationships between psychophysiological measures, expressive behaviour, and subjective emotional or affective response are considered.     

Gender, social competence, and symptomatology in schizophrenia: a longitudinal analysis

The relationship between gender and social skill measured by performance on a role play test was examined in a sample of 57 schizophrenics, 33 affective disorder patients, and 20 nonpatient controls. Female schizophrenics were more skilled than male schizophrenics, but no gender differences were present in the affective patients or the controls. Longitudinal analyses conducted on the schizophrenic group indicated that the superior social skill of women was stable over the year following a symptom exacerbation. Symptoms and social adjustment improved for both men and women over the year, but did not differ according to gender. The implications of the results for gender differences in the long-term outcome of schizophrenia are discussed.     

Patients with schizophrenia demonstrate dissociation between affective experience and motivated behavior

Self-reported emotional experience does not differ between patients with schizophrenia and healthy individuals, suggesting that the anhedonia in schizophrenia instead reflects decoupling of affect from motivated behavior. In 2 behavioral conditions, participants with schizophrenia and healthy participants were able to prolong or decrease exposure to stimuli while stimuli were present or alter the likelihood of future exposure to stimuli on the basis of internal representations. They also provided self-reports of affective experience. Patients showed weaker correspondence between behavior and ratings than did comparison participants. The effect was amplified when patients responded on the basis of internal rather than evoked stimulus representations. These data suggest that the motivational deficits in schizophrenia reflect problems in the ability to translate experience into action.     

Affective reactivity of language symptoms, startle responding, and inhibition in schizophrenia

The speech of some schizophrenia patients becomes markedly more disordered when negative affect is aroused. The authors tested associations between affective reactivity of speech and responsiveness and inhibition on an acoustic startle task in a sample of 27 outpatients. Patients whose language was reactive to negative affect showed significantly higher initial startle amplitudes than those whose language was not reactive. However, they also showed greater habituation to repeated startle stimuli over trials, even after differences in initial amplitudes were controlled statistically. These findings suggest that affective reactivity of speech is associated with higher initial startle responsiveness but also with greater habituation and, conversely, that patients who are relatively nonreactive to excitatory affective and sensory stimuli are also less reactive to inhibitory input.     

Left ear (right temporal hemisphere) advantage and left temporal hemispheric dysfunction in schizophrenia.

In this study, to investigate the right or left ear advantages in psychiatric patients. the durations of hearing for right and left ears were assessed in 61 psychiatric patients, 26 with schizophrenia, 17 with depressive disorder, 13 with bipolar affective disorder, and 5 with brief psychotic disorder, plus 24 controls. Diagnoses were made on the basis of information provided from clinical interviews and the Structured Clinical Interview for DSM-IV (SCID). Schizophrenia was associated with a left ear advantage, and both depressive disorder and brief psychotic disorder were associated with right ear advantage as well as controls. These results suggest that their schizophrenia may be associated with a left temporal lobe dysfunction.     

Optimizing treatment of schizophrenia. Enhancing affective/cognitive and depressive functioning

Recognition and treatment of schizophrenia has largely focused on positive symptoms of the disorder, such as delusions, hallucinations, and disorganization. However, other important symptoms, such as depression, cognition, and social functioning, have not received comparable attention. Fifty percent of schizophrenic patients suffer from comorbid depression, which is a major risk factor for suicide in this population, while 10% to 25% suffer from comorbid obsessive-compulsive disorder. Cognitive deficits commonly observed in patients with schizophrenia include problems with concentration, attention, and memory, as well as problem-solving and verbal skills. These deficits are observed at early stages of the illness and can predict deficits in functional capabilities, such as occupational and social skills, educational attainment, and the ability to live independently. The severity of such impairments affects all patient in this population, including up to 10% of patients working full time and up to one third of those working part time. In light of the debilitating effects of depression, cognitive impairment, and other aspects of affective functioning on the quality of life of patients with schizophrenia, physicians need to partner with their patients to address these concerns and determine an appropriate treatment regimen. This can be done with simple functional-based cognitive questioning, the use of evidence-based psychosocial practices, and psychoeducation on the many pharmacotherapeutic options. It is recommended that depressive or suicidal symptoms of schizophrenia be treated with an antidepressant or mood stabilizer only if the symptoms have not subsided after treatment of the psychosis with an atypical antipsychotic. Additionally, relative to older medications, atypicals have demonstrated benefit in improving some of the cognitive impairments.     

Concordance of the MCMI-II,the MMPI,and Axis I Discharge Diagnosis in Psychiatric Inpatients

Discriminant functions of the MMPI and the MCMI-II were compared in a sample of 166 hospitalized psychiatric patients with discharge diagnoses of affective disorder (63), schizophrenia (26), substance abuse (35), and other disorders (42). Of special interest was the comparative diagnostic utility of the two instruments in regards to DSM-III-R Axis I diagnoses, Both tests performed reasonably well in the discriminant function analyses; however, the MCMI-II achieved a somewhat superior overall hit rate with this sample of inpatients (79% to 68%). This difference was tied to greater accuracy of the MCMI-II for identifying the affective disorders group.     

Concordance of the MCMI-II, the MMPI, and Axis I discharge diagnosis in psychiatric inpatients.

Discriminant functions of the MMPI and the MCMI-II were compared in a sample of 166 hospitalized psychiatric patients with discharge diagnoses of affective disorder (63), schizophrenia (26), substance abuse (35), and other disorders (42). Of special interest was the comparative diagnostic utility of the two instruments in regards to DSM-III-R Axis I diagnoses. Both tests performed reasonably well in the discriminant function analyses; however, the MCMI-II achieved a somewhat superior overall hit rate with this sample of inpatients (79% to 68%). This difference was tied to greater accuracy of the MCMI-II for identifying the affective disorders group.     

Structural brain abnormalities in the major psychoses: a quantitative review of the evidence from computerized imaging

The neuroimaging literature on structural brain abnormalities in the major psychoses is quantitatively reviewed. The mean effect size for studies of lateral ventriculomegaly in schizophrenia (d = .70) corresponded to 43% nonoverlap between the distributions of schizophrenics and control Ss. Planimetry yielded larger effects than linear methods of ventricular size estimation. Although enlargement of the third ventricle was comparable to that of lateral ventriculomegaly (d = .66), it was found to be significantly greater after differences in measurement method were taken into account. The average cumulative length of hospitalization, adjusted for patients' age and duration of illness, predicted ventriculomegaly in schizophrenia. Studies on schizophrenia and affective disorder differed neither in the extent of reported ventriculomegaly nor in the amount of "cortical atrophy."     

Turning it Upside Down: Areas of Preserved Cognitive Function in Schizophrenia

Patients with schizophrenia demonstrate marked impairments on most clinical neuropsychological tests. These findings suggest that patients suffer from a generalized form of cognitive impairment, with little evidence of spared performance documented in several large meta-analytic reviews of the clinical literature. In contrast, we review evidence for relative sparing of aspects of attention, procedural memory, and emotional processing observed in studies that have employed experimental approaches adapted from the cognitive and affective neuroscience literature. These islands of preserved performance suggest that the cognitive deficits in schizophrenia are not as general as they appear to be when assayed with clinical neuropsychological methods. The apparent contradiction in findings across methods may offer important clues about the nature of cognitive impairment in schizophrenia. The documentation of preserved cognitive function in schizophrenia may serve to sharpen hypotheses about the biological mechanisms that are implicated in the illness.     

局限期小细胞肺癌放疗中预防野照射和累及野照射的疗效分析

局限期小细胞肺癌综合治疗中采用三维适型或调强放疗技术,按不同照射范围分为累及野照射和预防野照射2个组进行比较,分析不同照射野对预后的影响。 67例局限期小细胞肺癌患者,随机分为累及野照射组37例和预防野照射组30例。累及野照射组照射范围包括化疗前CT所见肿瘤及转移淋巴结范围,预防野照射组照射范围包括原发灶、同侧肺门、纵隔及锁骨上淋巴引流区。两组均采用三维适形或调强技术,放疗剂量为DT50Gy～66Gy/5周～6周。结果全组总有效率为82.1%,局部复发率为29.9%,远处转移率为56.7%,1年、2年、3年生存率分别为68.7%、36.2%和20.1%,分组比较以上指标均无显著性差异（P＞0.05）。而两组病例急性放射性肺炎和食道炎发生率分别为5.4%、16.7%和2.7%、20.0%,累及野照射食管炎发生率显著低于预防野（P＜0.05）。     

The relationship between cognitive inhibition and psychotic symptoms

Cognitive models of schizophrenia have highlighted deficits of inhibitory attentional processes as central to the disorder. This has been investigated using "negative priming" (S. P. Tipper, 1985), with schizophrenia patients showing a reduction of negative priming in a number of studies. This study attempted to replicate these findings, but studied psychotic symptoms rather than the broad diagnostic category of schizophrenia. Psychotic individuals exhibiting positive symptoms were compared with asymptomatic psychiatric patients and with a normal control group. As predicted, the symptomatic group failed to show the usual negative priming effect, which was present in the asymptomatic and normal groups. A modest but significant correlation was found between negative priming and delusions. Neither diagnosis, nor affective or negative symptoms, nor chronicity, nor medication, was related to negative priming. These data replicate previous findings that positive symptoms are related to a reduction in cognitive inhibition, although considerable variability was observed among the psychotic patients.     

Antipsychotika und sexuelle Dysfunktion

Antipsychotic drugs are used in the treatment of psychotic symptoms in schizophrenia and affective disorders. A direct correlation between increased dopaminergic activity and increased sexual desire and sexual activity is well documented in animal experiments and from observations in humans. Comparatively little researched and recognized is pharmacologically induced sexual dysfunction. In contrast to the antipsychotic effect and extrapyramidal motor side effects, no dose–response relationships are known for sexual side effects. This may be due to the fact that antipsychotics act at different levels in the sexual experience. Sexual dysfunction may be present on social, psychological, central nervous system and peripheral–organic levels, respectively. These levels are closely associated with each other and influence each other. Therefore, sexual dysfunction is generally a combination of dysfunctions at several of these levels. For a variety of reasons, there are no generally accepted standards for a healthy and fulfilling sex life. As a treating physician, the fact that sexual disorders are also not a rare phenomenon in mentally and physically healthy people should be kept in mind and that patients with schizophrenia regardless of the etiology of the sexual dysfunction may also benefit from sexual medicine or specific psychotherapeutic treatment.     

Approaches to Cognitive Remediation of Neuropsychological Deficits in Schizophrenia: A Review and Meta-Analysis

A review and critique of the literature pertaining to the use of cognitive remediation techniques in patients with schizophrenia is presented. The review is organized into three sections, according to the neuropsychological deficit targeted for remediation: 1) executive-function, 2) attention, and 3) memory. With regards to executive-function, despite an initial report suggesting that Wisconsin Card Sorting Test performance cannot be remediated, subsequent studies suggest that performance can be improved on a variety of dependent measures including perseverative errors, categories achieved, and conceptual level responses. These observations were confirmed by a meta-analytic investigation that revealed large mean effects sizes (d ₊ = 0.96) for these studies. Effect sizes were homogenous across discrepant remediation strategies and dependent measures. With regards to attention, serial scanning can be improved with instruction and reinforcement, whereas there is mixed evidence suggesting that practice-based attention drills can improve performance on measures of sustained attention in schizophrenia. With regards to memory, relatively simple semantic and affective elaborate encoding strategies elevates verbal list-learning memory in patients with schizophrenia to levels consistent with controls. A similar encoding procedure, combined with vigilance training, produces substantial improvement in social cue recognition. Avenues for future research are discussed.     

Update: new uses for lithium and anticonvulsants

Anticonvulsants are being used clinically as monotherapy and adjuncts in mental illnesses other than affective disorders. This review focuses on the literature for anticonvulsants and lithium in substance use disorders, anxiety disorders, and schizophrenia. Given the abuse potential and other difficulties with prescribing benzodiazepines for alcohol and benzodiazepine withdrawal, anticonvulsants have been considered as an alternative. Promising therapeutic effects have been demonstrated in many of the anxiety disorders, with the greatest number of trials and positive results in posttraumatic stress disorder. Although anticonvulsant and lithium augmentation for schizophrenia is common in practice and has been studied in double-blind, randomized, controlled trials, the sum of the evidence has been inconclusive.